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[膀胱癌的免疫疗法]

[Immunotherapy for Bladder Cancer].

作者信息

Büchler T

出版信息

Klin Onkol. 2017 Winter;30(Supplementum3):6-9. doi: 10.14735/amko20173S6.

Abstract

Urothelial carcinoma is the most common urological malignancy. Nonspecific immunotherapy using the Bacillus Calmette-Guerin vaccine has long been the mainstay for the treatment of high-risk superficial bladder carcinoma in an adjuvant setting after transurethral endoscopic resection. In metastatic disease, cisplatin-based chemotherapy remains the main therapeutic modality. In Europe, the standard second-line chemotherapy for patients with cisplatin-refractory tumours is vinflunine. Other systemic treatments with a lower level of evidence include paclitaxel and docetaxel. Studies of tumour microenvironment indicate a significant role for the immune system in the pathogenesis of urothelial tumours and the presence of a CD8 lymphocyte infiltrate is associated with better survival. In urothelial tumours, the correlation between PD-L1 expression in the tumour and the response to PD-1/PD-L1 inhibitors has been repeatedly demonstrated in clinical studies. Several inhibitors of PD-1/PD-L1 pathway are undergoing advanced-phase clinical trials and atezolizumab, nivolumab, pembrolizumab, durvalumab, and avelumab have already have received permanent or temporary registration status in the United States, mostly as second-line treatments for patients progressing on cisplatin-based chemotherapy. Three of these agents are currently registered in Europe: nivolumab for second line treatment and atezolizumab and pembrolizumab for first line treatment in patients not eligible for cisplatin as well as and for second line treatment. These novel immunotherapeutic agents for bladder cancer are relatively well tolerated and therefore potentially useful for patients with contraindications or intolerance to platinum regimens. The main toxicities include asthenia/fatigue, lymphopenia, anaemia, musculoskeletal pain, decreased appetite, and nausea.Key words: bladder cancer - imunotherapy - PD-1 receptor - antibodies - monoclonal This work was supported by the Czech Ministry of Health CR - RVO Thomayer Hospital - TN 0064190. The author declare he has no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 29. 8. 2017Accepted: 3. 10. 2017.

摘要

尿路上皮癌是最常见的泌尿系统恶性肿瘤。长期以来,使用卡介苗疫苗进行的非特异性免疫疗法一直是经尿道内镜切除术后辅助治疗高危浅表性膀胱癌的主要手段。在转移性疾病中,以顺铂为基础的化疗仍然是主要的治疗方式。在欧洲,对于顺铂难治性肿瘤患者,标准的二线化疗药物是长春氟宁。其他证据级别较低的全身治疗药物包括紫杉醇和多西他赛。肿瘤微环境研究表明,免疫系统在尿路上皮肿瘤的发病机制中起重要作用,CD8淋巴细胞浸润与更好的生存率相关。在尿路上皮肿瘤中,临床研究反复证明肿瘤中PD-L1表达与对PD-1/PD-L1抑制剂的反应之间存在相关性。几种PD-1/PD-L1通路抑制剂正在进行晚期临床试验,阿特珠单抗、纳武单抗、帕博利珠单抗、度伐鲁单抗和阿维鲁单抗在美国已获得永久或临时注册状态,主要作为接受基于顺铂化疗进展的患者的二线治疗药物。其中三种药物目前在欧洲已注册:纳武单抗用于二线治疗,阿特珠单抗和帕博利珠单抗用于不符合顺铂治疗条件患者的一线治疗以及二线治疗。这些用于膀胱癌的新型免疫治疗药物耐受性相对较好,因此对于有铂类方案禁忌或不耐受的患者可能有用。主要毒性包括乏力/疲劳、淋巴细胞减少、贫血、肌肉骨骼疼痛、食欲减退和恶心。关键词:膀胱癌 - 免疫疗法 - PD-1受体 - 抗体 - 单克隆 本研究得到捷克卫生部CR - RVO托马耶尔医院 - TN 0064190的支持。作者声明,他在研究中使用的药物、产品或服务方面不存在潜在利益冲突。编辑委员会声明,该手稿符合ICMJE关于生物医学论文的建议。提交日期:2017年8月29日 接受日期:2017年10月3日

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